1. Field of the Invention
The present invention relates generally to synaptic adhesion molecules and their role in pancreatic islet β-cells and, in particular, methods for imaging, isolating, and detecting the islets as well as inhibiting, treating and reversing diseases related to β-cell and pancreatic abnormalities.
2. Description of Related Art
Synaptic adhesion molecules are a disparate family of cell surface proteins involved in the adhesion of cells at synaptic junctions. The main constituents of synaptic adhesion molecules are members of the cadherin family and immunoglobulin superfamily. Synaptic adhesion molecules are thought to serve a plethora of functions, ranging from adhesion and cellular signaling to synaptic differentiation. Recent research has identified a synaptic adhesion molecule, SynCAM, as a molecule located at the synaptic junction. Two other known groups of synaptic adhesion molecules include neuroligins (e.g., neuroligin 1, neuroligin 2, neuroligin 3, neuroligin 4X and neuroligin 4Y) and neurexins (e.g., neurexin 1α, neurexin 2α, neurexin 3α, neurexin 1β, neurexin 2β, and neurexin 3β). The sequences of these polypeptides are known in the art and are available on the Internet at National Center for Biotechnology Information (“NCBI”).
As the incidence of diabetes increases, so too does the need for more improved diagnostic and treatment modalities. Islet β-cell transplantation has emerged as a key therapy in the treatment of type 1 diabetes. Although β-cell transplantation has met with some success, the treatment is fraught with numerous problems. Although, β-cell transplantation is initially effective for many patients, over time the recipient's ability to maintain insulin independence diminishes. The causes of this loss of independence are not known although a loss of β-cell mass is believed to be one cause. Because distinct β-cell specific cell surface proteins have not heretofore been identified, this has made determining the exact cause difficult.
The ability to measure islet β-cell mass in vivo is of great interest to researchers and clinicians alike. Cell-surface proteins specific enough to be targeted for imaging and treatment have not heretofore been obtained which has hindered research in the areas of pancreatic cancer and, especially, diabetes mellitus. There are no known cell surface markers expressed in islet, β-cells of the pancreas that are specific enough to β-cells to be used for imaging or treatment.